Mantle-Cell Lymphoma
Conditions
Keywords
Non-Hodgkin's Lymphoma
Brief summary
The investigator(s) hypothesize that Rituximab together with combination chemotherapy, followed by Rituximab maintenance therapy, will provide better disease control with improved response rates and overall survival in patients with previously untreated Mantle Cell Lymphoma (MCL).
Interventions
BIOLOGICALG-CSF
Granulocyte-colony stimulating factor (G-CSF) 480 mcg subcutaneously starting on Day 13 of Cycles 1 and 3; and Day 7 of Cycles 2 and 4.
DRUGRituximab
Rituximab 375 mg/m\^2 intravenously (IV) on Day 1 for 4 Cycles during induction therapy. Participants achieving complete remission will then receive Rituximab maintenance therapy every 6 months for up to three years.
DRUGCyclophosphamide
Cyclophosphamide 800 mg/m\^2 IV on Day 1 and 200 mg/m\^2 IV on Days 2 through 5 of Cycles 1 and 3.
DRUGCytarabine
Cytarabine (AraC) 2 grams/m\^2 IV on Days 1 and 2 of Cycles 2 and 4.
DRUGDoxorubicin
Doxorubicin 45 mg/m\^2 IV bolus on Day 1 of Cycles 1 and 3.
DRUGEtoposide
Etoposide (VP16) 60 mg/m\^2 IV on Days 1 through 5 of Cycles 2 and 4.
DRUGIfosfamide
Ifosfamide 1.5 grams/m\^2 IV on Days 1 through 5 of Cycles 2 and 4.
DRUGLeucovorin
Leucovorin 100 mg/m\^2 IV beginning 36 (+/-4) hours after start of Methotrexate infusion, and then 10 mg/m\^2 at 6 hour (+/- 30 min) intervals until Methotrexate level is \< 0.1 µmol/L during Cycles 1 and 3.
DRUGMesna
Mesna 360 mg/m\^2 IV on Days 1 through 5 of Cycles 2 and 4.
DRUGMethotrexate
Methotrexate (MTX) 1,200 mg/m\^2 in 250 mL with Dextrose 5% in water (D5W) IV over 1 hour, followed by Methotrexate 3,000 mg/m\^2 in 1,000 mL D5W by continuous infusion over 23 (+/-2) hours on Day 10 of Cycles 1 and 3.
DRUGVincristine
Vincristine 1.5 mg/m\^2 IV push (maximum of 2 mg) on Days 1 and 8 of Cycles 1 and 3.
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Previously untreated, histologically confirmed mantle cell lymphoma, 2. Measurable or evaluable disease (at least one site with \>1.5 cm in diameter 3. All stages are eligible 4. Age \> 18 years 5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 6. Adequate hepatic function: * Bilirubin \< 3 mg/dL * Transaminases (serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate-pyruvate transaminase (SGPT)) \< than 2.5 times the upper limit of normal for the institution, unless due to lymphomatous involvement 7. Serum creatinine\< 1.5 mg/dl 8. Ability to give informed consent 9. Women of childbearing potential must have a negative pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study. 10. Life expectancy greater than 6 months.
Exclusion criteria
1. Previous chemotherapy, immunotherapy or radiotherapy for this mantle cell lymphoma 2. Concurrent active malignancies, with the exception of in situ carcinoma of the cervix and basal cell carcinoma of the skin. 3. Grade 3 or 4 cardiac failure and/or ejection fraction \< 50. 4. Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol. 5. Patients with a known history of human immunodeficiency virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS). 6. Presence of hepatitis or hepatitis B virus (HBV) infection. 7. Pregnant or breast-feeding women. 8. Central Nervous System (CNS) involvement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 12 years | Progression-Free Survival (PFS) among study participants. PFS is defined as the time in years from start of treatment to the earliest one of the following events: relapse (in patients who achieve complete response), disease progression (in patients with partial response or stable disease), or death. PFS will be evaluated by treating physician from staging Computed Tomography (CT) or Positron Emission Tomography (PET) scans. |
| Progression-Free Survival (PFS) Rate at 5 Years Using Kaplan-Meier Method | 5 years | Progression-Free Survival (PFS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of participants alive without relapse or disease progression at 5 years after starting study therapy. PFS is defined as the time from start of treatment to the earliest one of the following events: relapse (in patients who achieve complete response), disease progression (in patients with partial response or stable disease), or death. PFS will be evaluated by treating physician from staging Computed Tomography (CT) or Positron Emission Tomography (PET) scans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Rate at 5 Years Using Kaplan-Meier Method | 5 years | Overall Survival (OS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of survival beyond 5 years. OS is defined as elapsed time from start date of treatment to date of death from any cause. Alive participants will be censored at last date known to be alive. |
| Rate of Response to Study Therapy | Up to 8 years | The rate of response to study therapy will be reported as the number of participants achieving complete response (CR), complete response/unconfirmed (CRu) or partial response (PR) to protocol therapy according to criteria assignable to Non-Hodgkin's Lymphoma (NHL). Response assessment will be done by CT and Positron emission tomography (PET) scans, and bone marrow biopsy/aspirate, if clinically indicated. |
| Number of Participants Experiencing Treatment-Related Serious Adverse Events During R-MACLO/IVAM Induction Therapy | Up to 4 months | The number of participants experiencing treatment-related serious adverse events (SAEs) during R-MACLO/IVAM induction therapy. AEs and SAEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0, as evaluated by treating physician. |
| Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy | Up to 4 months | The number of participants experiencing treatment-related adverse events (AEs) during R-MACLO/IVAM induction therapy. AEs and SAEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0, as evaluated by treating physician. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| R-MACLO/IVAM Group Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
* Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
* Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | R-MACLO/IVAM Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 25 |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 8 / 25 |
Outcome results
Primary
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) among study participants. PFS is defined as the time in years from start of treatment to the earliest one of the following events: relapse (in patients who achieve complete response), disease progression (in patients with partial response or stable disease), or death. PFS will be evaluated by treating physician from staging Computed Tomography (CT) or Positron Emission Tomography (PET) scans.
Time frame: Up to 12 years
Population: Participants that completed Cycles 1 and 2 of R-MACLO/IVAM induction therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R-MACLO/IVAM Group | Progression-Free Survival (PFS) | 8 years |
Primary
Progression-Free Survival (PFS) Rate at 5 Years Using Kaplan-Meier Method
Progression-Free Survival (PFS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of participants alive without relapse or disease progression at 5 years after starting study therapy. PFS is defined as the time from start of treatment to the earliest one of the following events: relapse (in patients who achieve complete response), disease progression (in patients with partial response or stable disease), or death. PFS will be evaluated by treating physician from staging Computed Tomography (CT) or Positron Emission Tomography (PET) scans.
Time frame: 5 years
Population: Participants that completed Cycles 1 and 2 of R-MACLO/IVAM induction therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-MACLO/IVAM Group | Progression-Free Survival (PFS) Rate at 5 Years Using Kaplan-Meier Method | 57.1 percentage probability at 5 years |
Secondary
Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy
The number of participants experiencing treatment-related adverse events (AEs) during R-MACLO/IVAM induction therapy. AEs and SAEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0, as evaluated by treating physician.
Time frame: Up to 4 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| R-MACLO/IVAM Group | Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy | Grade 1 and 2 AEs | 25 Participants |
| R-MACLO/IVAM Group | Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy | Grade 3 or higher AEs | 24 Participants |
Secondary
Number of Participants Experiencing Treatment-Related Serious Adverse Events During R-MACLO/IVAM Induction Therapy
The number of participants experiencing treatment-related serious adverse events (SAEs) during R-MACLO/IVAM induction therapy. AEs and SAEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0, as evaluated by treating physician.
Time frame: Up to 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| R-MACLO/IVAM Group | Number of Participants Experiencing Treatment-Related Serious Adverse Events During R-MACLO/IVAM Induction Therapy | 2 Participants |
Secondary
Overall Survival (OS) Rate at 5 Years Using Kaplan-Meier Method
Overall Survival (OS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of survival beyond 5 years. OS is defined as elapsed time from start date of treatment to date of death from any cause. Alive participants will be censored at last date known to be alive.
Time frame: 5 years
Population: Participants that completed Cycles 1 and 2 of R-MACLO/IVAM induction therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-MACLO/IVAM Group | Overall Survival (OS) Rate at 5 Years Using Kaplan-Meier Method | 79.7 percentage probability at 5 years |
Secondary
Rate of Response to Study Therapy
The rate of response to study therapy will be reported as the number of participants achieving complete response (CR), complete response/unconfirmed (CRu) or partial response (PR) to protocol therapy according to criteria assignable to Non-Hodgkin's Lymphoma (NHL). Response assessment will be done by CT and Positron emission tomography (PET) scans, and bone marrow biopsy/aspirate, if clinically indicated.
Time frame: Up to 8 years
Population: Participants that completed Cycles 1 and 2 of R-MACLO/IVAM induction therapy and evaluated for response.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| R-MACLO/IVAM Group | Rate of Response to Study Therapy | Complete Response (CR) | 20 Participants |
| R-MACLO/IVAM Group | Rate of Response to Study Therapy | Complete Response unconfirmed (CRu) | 0 Participants |
| R-MACLO/IVAM Group | Rate of Response to Study Therapy | Partial Response (PR) | 2 Participants |